FAT4 identified as a potential modifier of orofacial cleft laterality

Year: 2021

Type: article

Abstract: Orofacial clefts (OFCs) are common (1 in 700 births) congenital malformations that include cleft lip (CL) and cleft lip and palate (CLP). These OFC subtypes are also heterogeneous themselves, with the cleft lip occurring on the left, right, or both sides of the upper lip. Unilateral CL and CLP have a 2:1 bias towards left-sided clefts, suggesting a nonrandom process. Here, we performed a study of left- and right-sided clefts within the CL and CLP subtypes to better understand the genetic factors controlling cleft laterality. We conducted genome-wide modifier analyses by comparing cases that had right unilateral CL (RCL; N=130), left unilateral CL (LCL; N=216), right unilateral CLP (RCLP; N=416), or left unilateral CLP (LCLP; N=638), and identified a candidate region on 4q28, 400 kb downstream from FAT4 , that approached genome-wide significance for LCL vs. RCL (p = 8.4×10 −8 ). Consistent with its potential involvement as a genetic modifier of cleft lip, we found that Fat4 exhibits a specific domain of expression in the mesenchyme of the medial nasal processes that form the median upper lip. Overall, these results suggest that the epidemiological similarities in left-to right-sided clefts in CL and CLP are not reflected in the genetic association results.

Source: Genetic Epidemiology

DOI: 10.1002/gepi.22420

Authors: Sarah W. Curtis, Daniel Chang, Miranda R. Sun, Michael P. Epstein, Jeffrey C. Murray, Eleanor Feingold, Terri H. Beaty, Seth M. Weinberg, Mary L. Marazita, Robert J. Lipinski, Jenna C. Carlson, Elizabeth J. Leslie

Institutions: Emory University, University of Wisconsin–Madison, University of Iowa, University of Pittsburgh, Johns Hopkins University

Language: English

Topic: Cleft Lip and Palate Research

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: University of Washington, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Dental and Craniofacial Research

OpenAlex ID: W3165990017